Chromosome Gene Orientation Inversion Networks (GOINs) of Plasmodium Proteome

Abstract

The spatial distribution of genes in chromosomes seems not to be random. For instance, only 10% of genes are transcribed from bidirectional promoters in humans, and many more are organized into larger clusters. This raises intriguing questions previously asked by different authors. We would like to add a few more questions in this context, related to gene orientation inversions. Does gene orientation (inversion) follow a random pattern? Is it relevant to biological activity somehow? We define a new kind of network coined as the gene orientation inversion network (GOIN). GOIN's complex network encodes short- and long-range patterns of inversion of the orientation of pairs of gene in the chromosome. We selected Plasmodium falciparum as a case of study due to the high relevance of this parasite to public health (causal agent of malaria). We constructed here for the first time all of the GOINs for the genome of this parasite. These networks have an average of 383 nodes (genes in one chromosome) and 1314 links (pairs of gene with inverse orientation). We calculated node centralities and other parameters of these networks. These numerical parameters were used to study different properties of gene inversion patterns, for example, distribution, local communities, similarity to Erdös-Rényi random networks, randomness, and so on. We find clues that seem to indicate that gene orientation inversion does not follow a random pattern. We noted that some gene communities in the GOINs tend to group genes encoding for RIFIN-related proteins in the proteome of the parasite. RIFIN-like proteins are a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Consequently, we used these centralities as input of machine learning (ML) models to predict the RIFIN-like activity of 5365 proteins in the proteome of Plasmodium sp. The best linear ML model found discriminates RIFIN-like from other proteins with sensitivity and specificity 70-80% in training and external validation series. All of these results may point to a possible biological relevance of gene orientation inversion not directly dependent on genetic sequence information. This work opens the gate to the use of GOINs as a tool for the study of the structure of chromosomes and the study of protein function in proteome research.

IFPTML Mapping of Drug Graphs with Protein and Chromosome Structural Networks vs. Pre-Clinical Assay Information for Discovery of Antimalarial Compounds

“…This information has been found to be somehow relevant to the biological activity of some proteins in Pf proteome. Consequently, in this work we also used the Chromosome Gene Orientations Inversion Networks (GOINs) of Pf proteome assembled with P ik and O ik information in a previous work [ 29 ].…”

“…In previous work, we analyzed the proteome/genome and chromosomes of Pf using data from NCBI-GDV and UniProt databases [ 29 ]. However, this previous work has not considered the possibility of mapping this data vs. preclinical assays of compounds towards the design of new Antimalarials.…”

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